Polymorphism of Cyclic Dinucleotides
Polymorphism of Cyclic Dinucleotides
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Date
2015
Authors
Roembke, Benjamin Thompson
Advisor
Sintim, Herman O.
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Abstract
Cyclic dinucleotides such as cyclic dimeric guanosine monophosphate (c-di-GMP,) cyclic dimeric adenosine monophosphate (c-di-AMP) and cyclic guanosine-adenosine monophosphate (cGAMP) are found in both prokaryotes and eukaryotes and are important in cell signaling processes. The work discussed herein aims at understanding the aggregative properties of these cyclic dinucleotides for interest in the biological implications of aggregation and for the purpose of various applications of these higher order structures. The applications include simple detection methods for these molecules as well as a unique G-quadruplex peroxidase that can be used for catalysis. To that end, a new fluorescent cyclic dinucleotide which incorporated the fluorescent purine analog, 2-aminopurine, was synthesized. This analog is capable of forming intercalated dimers with natural cyclic dinucleotides containing guanine which allows for a simple turn-off fluorescent method for these second messengers. Additionally, ligands containing four guanine bases were utilized to bind c-di-GMP and leading to a fluorescent turn-on fluorescent detection method. The c-di-GMP octamer was also studied for its ability to enhance the peroxidation ability of the iron-containing cofactor hemin. Its proficient ability to enhance catalysis suggests that DNA loops found in other G-quadruplex forming molecules are not necessary for catalytic enhancement of hemin.